Brain injury is a frequent comorbidity in chronically ventilated preterm infants. However, the molecular basis of the brain injury remains incompletely understood. This article discusses the subtle (diffuse) form of brain injury that has white matter and gray matter lesions without germinal matrix hemorrhage-intraventricular hemorrhage, posthemorrhagic hydrocephalus, or cystic periventricular leukomalacia. This article synthesizes data that suggest that diffuse lesions to white matter and gray matter are collateral damage related to ventilator strategy. Evidence is introduced from the 2 large-animal, physiologic models of evolving neonatal chronic lung disease that suggest that an epigenetic mechanism may underlie the collateral damage.